Mycophenolate mofetil was associated with stabilization or improvement of predicted forced vital capacity in patients with connective tissue disease-associated interstitial lung disease. Moreover, the drug was safe and well tolerated in this population over a median 2.5 years of use, according to a study published online in the Journal of Rheumatology.
Dr. Aryeh Fischer of the autoimmune and interstitial lung disease program at National Jewish Health in Denver and colleagues looked at the medical records of all patients who received mycophenolate mofetil (MMF) and were treated by an interstitial lung disease specialist at his facility between January 2008 and January 2011.
Dr. Aryeh Fischer
In total, 125 of these patients had connective tissue disease–associated interstitial lung disease (CTD-ILD), plus 6 months of follow-up data (J. Rheumatol. 1 Mar. 2013 [doi:10.3899/jrheum.121043]).
Patients’ mean age was 60.4 years; 42% were female and 83% were white.
A total of 44 of these patients had systemic sclerosis, 32 had polymyositis/dermatomyositis, 19 had lung-dominant connective tissue disease, 18 had rheumatoid arthritis, 5 had Sjögren disease, 4 had systemic lupus erythematosus, and 3 had mixed connective tissue disease.
Most subjects took 3,000 mg/day (65%) of MMF, with none exceeding that dosage and only four subjects taking less than 2,000 mg/day.
Overall, the authors reported that, over a median duration of MMF use of 897 days (2.5 years), only 13 subjects discontinued the drug, citing gastrointestinal intolerance, ILD progression, hepatic transaminase elevation, recurrent infections, and cytopenias.
Even among those who discontinued the drug, however, the median duration of use was still more than 2 years, at 763 days.
Dr. Fischer and his associates then looked at changes in pulmonary physiology. Over the 156 weeks prior to MMF initiation, a mixed-effects model of the entire cohort showed no significant changes in either estimated percentage of predicted forced vital capacity for sex, ethnicity, age, and height (FVC%) or the estimated percentage of predicted diffusing capacity for sex, ethnicity, age, and height (DLCO%).
At 52 weeks, however, there was a mean increase in FVC% of 4.9% (P = .01) and of DLCO% of 6.3% (P = .02), they reported. At 104 weeks after initiation of MMF, the change in FVC% had increased to 6.1% (P = .0008), and at 156 weeks, it had improved 7.3% from baseline (P = .004).
Similarly, by 104 weeks, the DLCO% had increased by 7.1% (P = .01); at 156 weeks, there was a mean 7.8% change from baseline (P = .05).
Patients taking MMF were able to taper prednisone doses once they initiated the drug, Dr. Fischer and his associates wrote.
Indeed, according to the researchers, model estimates for mean daily prednisone doses for the entire cohort at 52 and 26 weeks before MMF initiation were 14 and 7 mg, respectively. At MMF initiation, the mean dose was 20 mg/day.
In contrast, "estimated prednisone dose at 26 and 52 weeks after MMF initiation was 12 and 5 mg, respectively (P less than .0001 for each, compared to 20 mg at MMF initiation)," they calculated.
Dr. Fischer and his associates conceded several limitations to their study, including its retrospective design.
"From our data, one cannot know whether treatment with other immunosuppressive agents would yield similar results or even whether MMF definitively caused the observed changes in FVC% and DLCO%," they wrote.
"However, it is telling that MMF was well tolerated and efficacious and allowed for corticosteroid tapering," they added. "Prospective studies of MMF are indicated to further define the role of MMF in the treatment of CTD-ILD."
In an e-mail, Dr. Fischer stated that he had no industry disclosures relevant to the current study. He added that he and several coinvestigators are also involved with the Scleroderma Lung Study II, which is investigating mycophenolate mofetil versus oral cyclophosphamide in scleroderma interstitial lung disease and has no industry sponsorship. The present study was partially funded by a grant to one of the investigators from the National Institutes of Health.